Summary of Work: Three adhesion receptor families appear to be important in mediating pulmonary leukocyte trafficking. The select family of receptors initiates early leukocyte/ endothelial interactions, while the integrin and immunoglobulin families interact in later adhesion reactions. We previously found that monoclonal antibodies (MAb's) directed against the integrin family of adhesion molecules limited pulmonary injury and improved survival after tumor necrosis factor challenge in canines. However, administration of integrin MAb's during bacterial peritonitis in a canine model reduced serum endotoxin clearance and worsened cardiovascular function and survival. During pulmonary infection in rats, similar MAb's were beneficial in limiting pulmonary injury, but still worsened survival. In additional studies we showed that intercellular adhesion molecule 1(ICAM-1)-directed MAb's were also harmful during intrapulmonary infection. These studies have emphasized the importance of both integrin and ICAM-1 adhesion receptors in host defense during pneumonia. To complete these studies, we investigated the effects of MAb's directed against L-selectin, a member of the third family of adhesion receptors. Although improving survival with intravascular E. coli challenge in this study, L-selectin-directed MAb worsened survival with pulmonary infection. In our studies, therefore, inhibiting leukocyte-endothelial interaction occurring either early via selectins or later via integrins and ICAM's, worsened outcome of intrapulmonary gram-negative infection.